H1R expression by CD11B+ cells is not required for susceptibility to experimental allergic encephalomyelitis

Abstract

The histamine H1 receptor (Hrh1/H1R) was identified as an autoimmune disease gene in experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS). Previously, we showed that selective re-expression of H1R by endothelial cells or T cells in H1RKO mice significantly reduced or complemented EAE severity and cytokine responses, respectively. H1R regulates innate immune cells, which in turn influences peripheral and central nervous system CD4+ T cell effector responses. Therefore, we selectively re-expressed H1R in CD11b+ cells of H1RKO mice to test the hypothesis that H1R signaling in these cells contributes to EAE susceptibility. We demonstrate that transgenic re-expression of H1R by H1RKO-CD11b+ cells neither complements EAE susceptibility nor T cell cytokine responses highlighting the cell-specific effects of Hrh1 in the pathogenesis of EAE and MS, and the need for cell-specific targeting in optimizing therapeutic interventions based on such genes.